title: Impairments in site-specific AS160 phosphorylation and effects of exercise training.
abstract: The purpose of this study was to determine if site-specific phosphorylation at the level of Akt substrate of 160 kDa (AS160) is altered in skeletal muscle from sedentary humans across a wide range of the adult life span (18-84 years of age) and if endurance- and/or strength-oriented exercise training could rescue decrements in insulin action and skeletal muscle AS160 phosphorylation. A euglycemic-hyperinsulinemic clamp and skeletal muscle biopsies were performed in 73 individuals encompassing a wide age range (18-84 years of age), and insulin-stimulated AS160 phosphorylation was determined. Decrements in whole-body insulin action were associated with impairments in insulin-induced phosphorylation of skeletal muscle AS160 on sites Ser-588, Thr-642, Ser-666, and phospho-Akt substrate, but not Ser-318 or Ser-751. Twelve weeks of endurance- or strength-oriented exercise training increased whole-body insulin action and reversed impairments in AS160 phosphorylation evident in insulin-resistant aged individuals. These findings suggest that a dampening of insulin-induced phosphorylation of AS160 on specific sites in skeletal muscle contributes to the insulin resistance evident in a sedentary aging population and that exercise training is an effective intervention for treating these impairments.
authors.affiliation: Department of Biomedical Sciences, Ohio Musculoskeletal and Neurological Institute, Diabetes Institute, Ohio University, Athens, Ohio.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Consitt
authors.forename: Jessica
authors.initials: J
authors.lastname: Van Meter
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Newton
authors.forename: David N
authors.initials: DN
authors.lastname: Collier
authors.forename: Moahad S
authors.initials: MS
authors.lastname: Dar
authors.forename: Jørgen F P
authors.initials: JF
authors.lastname: Wojtaszewski
authors.forename: Jonas T
authors.initials: JT
authors.lastname: Treebak
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Tanner
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Houmard
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D015153:Blotting, Western; D003430:Cross-Sectional Studies; D005260:Female; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D000078723:Nuclear Receptor Interacting Protein 1; D010766:Phosphorylation; D010807:Physical Endurance; D055070:Resistance Training; D057185:Sedentary Behavior; D012694:Serine; D015398:Signal Transduction; D013912:Threonine
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020690:GTPase-Activating Proteins; D007328:Insulin; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; C518767:TBC1D4 protein, human; D013912:Threonine; D012694:Serine